14 september 2022: lees ook dit artikel: https://kanker-actueel.nl/hypec-hyperthermische-intraperitoneale-chemotherapie-met-mitomycine-c-naast-operatie-voor-lokaal-gevorderde-darmkanker-stadium-iv-verbetert-ziektecontrole-met-10-procent-op-3-jaars-meting.html

28 januari 2021: Bron: The Lancet

Altijd is gedacht dat een HIPEC = hyperthermische intraperitoneale chemotherapie naast een operatie van uitgezaaide darmkanker met uitzaaiingen in het buikvlies de overall overleving zou verbeteren. Zo wordt een HIPEC bij in het buikvlies uitgezaaide eierstokkanker gezien als de enige genezende behandeling bij dat stadium van de ziekte. Echter nu blijkt uit een grote langjarige Europese studie waaraan ook diverse Nederlandse ziekenhuizen deelnamen dat op oxaliplatine gebaseerde hyperthermische intraperitoneale chemotherapie (HIPEC) tijdens een zogeheten cytoreductieve chirurgie = een operatie waarbij zoveel mogelijk tumorweefsel wordt weggehaald en het buikvlies wordt schoongeschraapt geen extra overall overleving laat zien bij in het buikvlies uitgezaaide darmkanker.

De mediane overall overleving was na mediane follow-up van 63,8 maanden (IQR 53,0-77,1) 41,7 maanden (95% BI 36,253,8) in de cytoreductieve chirurgie plus HIPEC-groep en 41,2 maanden (35 · 1-49 · 7) in de groep met alleen cytoreductieve chirurgie (hazard ratio 1 · 00 [95 · 37% BI 0 · 63-1 · 58]; gestratificeerde log-rank p = 0 · 99).

Het percentage postoperatieve complicaties na 60 dagen was hoger met een HIPEC. (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).

Het studierapport is gepubliceerd in The Lancet:

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial

Published:January 18, 2021DOI:https://doi.org/10.1016/S1470-2045(20)30599-4



The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.


We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m 2) or open (460 mg/m 2) abdomen techniques, and systemic chemotherapy (400 mg/m 2 fluorouracil and 20 mg/m 2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.govNCT00769405, and is now completed.


Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).


Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.


Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.


  1. 1.
    • Segelman J 
    • Granath F 
    • Holm T 
    • Machado M 
    • Mahteme H 
    • Martling A
    Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer.
    Br J Surg. 2012; 99699-705
  2. 2.
    • Franko J 
    • Shi Q 
    • Goldman CD 
    • et al.
    Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of North Central Cancer Treatment Group phase III trials N9741 and N9841.
    J Clin Oncol. 2012; 30263-267
  3. 3.
    • Franko J 
    • Shi Q 
    • Meyers JP 
    • et al.
    Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.
    Lancet Oncol. 2016; 171709-1719
  4. 4.
    • Koga S 
    • Hamazoe R 
    • Maeta M 
    • Shimizu N 
    • Kanayama H 
    • Osaki Y
    Treatment of implanted peritoneal cancer in rats by continuous hyperthermic peritoneal perfusion in combination with an anticancer drug.
    Cancer Res. 1984; 441840-1846
  5. 5.
    • Elias D 
    • Detroz B 
    • Debaene B 
    • et al.
    Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia: reliable and unreliable concepts.
    Hepatogastroenterology. 1994; 41207-213
  6. 6.
    • Quenet F 
    • Goéré D 
    • Mehta SS 
    • et al.
    Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis.
    Ann Surg. 2011; 254294-301
  7. 7.
    • Elias D 
    • Gilly F 
    • Boutitie F 
    • et al.
    Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study.
    J Clin Oncol. 2009; 2863-68
  8. 8.
    • Verwaal VJ 
    • van Ruth S 
    • de Bree E 
    • et al.
    Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.
    J Clin Oncol. 2003; 213737-3743
  9. 9.
    • Goéré D 
    • Malka D 
    • Tzanis D 
    • et al.
    Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy?.
    Ann Surg. 2013; 2571065-1071
  10. 10.
    • Glehen O 
    • Cotte E 
    • Kusamura S 
    • et al.
    Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion.
    J Surg Oncol. 2008; 98242-246
  11. 11.
    • Glehen O 
    • Kwiatkowski F 
    • Sugarbaker PH 
    • et al.
    Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.
    J Clin Oncol. 2004; 223284-3292
  12. 12.
    • Elias D 
    • Lefevre J 
    • Chevalier J 
    • et al.
    Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.
    J Clin Oncol. 2009; 27681-685
  13. 13.
    • Chua TC 
    • Yan TD 
    • Saxena A 
    • Morris DL
    Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systematic review of morbidity and mortality.
    Ann Surg. 2009; 249900-907
  14. 14.
    • Foster JM 
    • Sleightholm R 
    • Patel A 
    • et al.
    Morbidity and mortality rates following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy compared with other high-risk surgical oncology procedures.
    JAMA Netw Open. 2019; 2e186847
  15. 15.
    • Elias D 
    • Bonnay M 
    • Puizillou JM 
    • et al.
    Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution.
    Ann Oncol. 2002; 13267-272
  16. 16.
    • Glehen O 
    • Gilly FN 
    • Boutitie F 
    • et al.
    Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1290 patients.
    Cancer. 2010; 1165608-5618
  17. 17.
    • Esquis P 
    • Consolo D 
    • Magnin G 
    • et al.
    High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis.
    Ann Surg. 2006; 244106-112
  18. 18.
    • Goere D 
    • Glehen O 
    • Quenet F 
    • et al.
    Results of a randomized phase 3 study evaluating the potential benefit of a second-look surgery plus HIPEC in patients at high risk of developing colorectal peritoneal metastases—PROPHYLOCHIP.
    Proc Am Soc Clin Oncol. 2018; 363531
  19. 19.
    • Klaver CEL 
    • Wisselink DD 
    • Punt CJA 
    • et al.
    Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial.
    Lancet Gastroenterol Hepatol. 2019; 4761-770
  20. 20.
    • Levine EA 
    • Stewart JH 
    • Shen P 
    • Russell GB 
    • Loggie BL 
    • Votanopoulos KI
    Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1000 patients.
    J Am Coll Surg. 2014; 218573-585
  21. 21.
    • Van Driel WJ 
    • Koole SN 
    • Sikorska K 
    • et al.
    Hyperthermic intraperitoneal chemotherapy in ovarian cancer.
    N Engl J Med. 2018; 378230-240
  22. 22.
    • Kirstein MN 
    • Root SA 
    • Moore MM 
    • et al.
    Exposure-response relationships for oxaliplatin-treated colon cancer cells.
    Anticancer Drugs. 2008; 1937-44
  23. 23.
    • Lemoine L 
    • Thijssen E 
    • Carleer R 
    • Geboers K 
    • Sugarbaker P 
    • van der Speeten K
    Body surface area-based vs concentration-based perioperative intraperitoneal chemotherapy after optimal cytoreductive surgery in colorectal peritoneal surface malignancy treatment: COBOX trial.
    J Surg Oncol. 2019; 119999-1010
  24. 24.
    • De Gramont A 
    • Figer A 
    • Seymour M 
    • et al.
    Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.
    J Clin Oncol. 2000; 182938-2947
  25. 25.
    • André T 
    • Boni C 
    • Navarro M 
    • et al.
    Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial.
    J Clin Oncol. 2009; 273109-3116
  26. 26.
    • Yurttas C 
    • Hoffmann G 
    • Tolios A 
    • et al.
    Systematic review of variations in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis from colorectal cancer.
    J Clin Med. 2018; 7567
  27. 27.
    • Hompes D 
    • D'Hoore A 
    • Wolthuis A 
    • et al.
    The use of oxaliplatin or mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study.
    J Surg Oncol. 2014; 109527-532
  28. 28.
    • Leung V 
    • Huo YR 
    • Liauw W 
    • Morris DL
    Oxaliplatin versus mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis.
    Eur J Surg Oncol. 2017; 43144-149
  29. 29.
    • Cavaliere F 
    • De Simone M 
    • Virzi S 
    • et al.
    Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study SITILO.
    Eur J Surg Oncol. 2011; 37148-154
  30. 30.
    • Prada-Villaverde A 
    • Esquivel J 
    • Lowy AM 
    • et al.
    The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery.
    J Surg Oncol. 2014; 110779-785
  31. 31.
    • Machover D 
    • Diaz-Rubio E 
    • de Gramont A 
    • et al.
    Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines.
    Ann Oncol. 1996; 795-98
  32. 32.
    • Andreou A 
    • Kopetz S 
    • Maru DM 
    • et al.
    Adjuvant chemotherapy with FOLFOX for primary colorectal cancer is associated with increased somatic gene mutations and inferior survival in patients undergoing hepatectomy for metachronous liver metastases.
    Ann Surg. 2012; 256642-650

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